Haemophagocytic lymphohistiocytosis MedDRA version: 19.0 Level: SOC Classification code 10010331 Term: Congenital, familial and genetic disorders System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Sponsors
NovImmune SA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Primary HLH patients of both genders, up to and including 18 years at diagnosis of HLH, or at an age appropriate to be treated in the investigator's practice. The diagnosis must be made on the following criteria (as per HLH-2004 protocol): a. A molecular diagnosis or familial history consistent with primary HLH OR b. 5 out of 8 criteria below are fulfilled: - Fever - Splenomegaly - Cytopenias affecting 2 of 3 lineages in the peripheral blood (hemoglobin 3mmol/L or >265mg/dL) and/or hypofibrinogenemia (=1.5g/L) - Hemophagocytosis in bone marrow, spleen or lymph nodes, with no evidence of malignancy - Low or absent natural killer (NK)-cell activity - Ferritin =500µg/L - Soluble CD25 (sCD25; i.e. soluble IL-2 receptor) =2400U/mL 2. Presence of active disease in patients as assessed by the treating physician 3. Patients having already received HLH conventional therapy must fulfill one of the following criteria as assessed by the treating physician: - Having not responded - Having not achieved a satisfactory response - Having not maintained a satisfactory response - Showing intolerance of conventional HLH treatment At the time of enrollment, eligible patients might still be receiving treatment (induction or maintenance) or might have discontinued it. 4. Informed consent signed by the patient (if =18 years old) or by their legally authorized representative(s) with the assent of patients who are legally capable of providing it. 5. Having received guidance on contraception for both male and female patients sexually active and having reached puberty: Females of child-bearing potential, having a negative pregnancy test at screening, and unless true abstinence is in line with the preferred and usual lifestyle of the patient, must agree to use two adequate methods of birth control from screening until 6 months after receiving last dose of the study drug, in addition to their partners using a barrier method. Acceptable forms of contraception are as follows: • Barrier methods: condoms, diaphragms, cervical caps; • Hormonal contraceptives: combination or progesterone only; • Includes depot contraceptives; • Intrauterine methods: intrauterine devices or systems. Males with partners(s) of child-bearing potential must agree to take appropriate precautions to avoid fathering a child from screening until 6 months after receiving last dose of the study drug and agree to use barrier contraception in addition to their partner(s) using another method. Are the trial subjects under 18? yes Number of subjects for this age range: 35 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 3 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Diagnosis of secondary HLH consequent to a proven rheumatic or neoplastic disease. 2. Body weight < 3 kg. 3. Patients treated with: - any T-cell depleting agents (such as anti-thymocyte globulin [ATG], anti-CD52) during the previous 2 weeks prior to screening - any other biologic drug within 5 times their defined half-life period, expect for rituximab in case of documented B-cell EBV infection 4. Active mycobacteria, Histoplasma Capsulatum,Shigella, Campylobacter, Leishmania or Salmonella infections. 5. Evidence of past history of tuberculosis or of latent tuberculosis. 6. Positive serology for HIV antibodies, hepatitis B surface antigen or hepatitis C antibodies. 7. Presence of malignancy. 8. Patient who have another concomitant disease or malformation severely affecting the cardiovascular, pulmonary, liver or renal function. 9. History of hypersensitivity or allergy to any components of the study regimen. 10. Vaccination with a live or attenuated live (including BCG) vaccine within the previous 12 weeks prior to screening. 11. Pregnant or lactating female patients.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To determine the safety and tolerability profile of multiple IV administrations of NI-0501 • To determine the efficacy and benefit/risk profile of NI-0501 in HLH patients • To describe the pharmacokinetic (PK) profile of NI-0501 in HLH patients • To define an appropriate NI-0501 therapeutic dose regimen for HLH • To determine the PD effects (levels of circulating Total IFN? and biomarkers of its neutralization, namely CXCL9 and CXCL10) •To determine other biomarkers, e.g. sCD25, IL-10 • To assess the immunogenicity of NI-0501;Secondary Objective: Not applicable;Primary end point(s): • Primary efficacy endpoint: - Overall response Rate, i.e. achievment of either Complete or Partial response of HLH Improvement at End of Treatment (EoT);Timepoint(s) of evaluation of this end point: See E.5.1. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Secondary efficacy endpoints: - Time to Response any time during the study - Durability of Response, i.e. maintenance of response achieved any time during the study until EoT and beyond (including data collected in the long-term follow-up study NI-0501-05) - Number of patients who reduce glucocorticoids by 50% or more of the baseline dose - Number of patients able to proceed to HSCT, when deemed indicated - Survival at Week 8 (or EoT) and at the end of the study • Other parameters: - Blood concentration of NI-0501 to determine NI-0501 pharmacokinetics in patients (TP1 - each visit, TP2 - end of treatment visit) - Determination of pharmacodynamic effects (levels of circulating IFN? and other biomarkers (TP1 - each visit, TP2 - end of treatment visit) • Safety and tolerability of multiple IV infusions of NI-0501 will be assessed as follows: - Incidence, severity, causality and outcomes of Adverse Events (serious and non-serious), with particular attention being paid to infections - Evolution of laboratory parameters such as complete blood cell count (CBC), with a focus on red cells (haemoglobin), neutrophils and platelets, liver tests, renal function tests and coagulation (Treatment period (TP) 1 - mandatory on Days 3 and 6, TP2 every 6-7 days) - Number of patients withdrawn for safety issues - Level (if any) of circulating antibodies against NI-0501 to determine immunogenicity; i.e. the development of anti-drug antibodies (ASAs) (TP2 - End of treatment visit) • Safety parameters to be collected and assessed: - Incidence, severity, causality and outcomes of Adverse Events (serious and non-serious), with particular attention being paid to infections;Timepoint(s) of evaluation of this end point: See E.5.2. | — |
Countries
Austria, Czech Republic, Germany, Italy, Spain, Sweden, Turkey, United Kingdom, United States
Contacts
Public ContactIsabelle Fournet
NovImmune SA
Outcome results
None listed